SLC6A5 solute carrier family 6 member 5 [Homo sapiens (human)] - Gene

Summary

Official Symbol: SLC6A5provided by HGNC
Official Full Name: solute carrier family 6 member 5provided by HGNC
Primary source: HGNC:HGNC:11051
See related: Ensembl:ENSG00000165970 MIM:604159; AllianceGenome:HGNC:11051
Gene type: protein coding
RefSeq status: REVIEWED
Organism: Homo sapiens
Lineage: Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae; Homo
Also known as: NET1; GLYT2; HKPX3; GLYT-2
Summary: This gene encodes a sodium- and chloride-dependent glycine neurotransmitter transporter. This integral membrane glycoprotein is responsible for the clearance of extracellular glycine during glycine-mediated neurotransmission. This protein is found in glycinergic axons and maintains a high presynaptic pool of neurotransmitter at glycinergic synapses. Mutations in this gene cause hyperekplexia; a heterogenous neurological disorder characterized by exaggerated startle responses and neonatal apnea. Two transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Jan 2016]
Expression: Low expression observed in reference dataset See more
Orthologs: mouse all
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Genomic context

Location:: 11p15.1

Exon count:: 17

Annotation release	Status	Assembly	Chr	Location
RS_2024_08	current	GRCh38.p14 (GCF_000001405.40)	11	NC_000011.10 (20599608..20659285)
RS_2024_08	current	T2T-CHM13v2.0 (GCF_009914755.1)	11	NC_060935.1 (20720301..20780085)
RS_2024_09	previous assembly	GRCh37.p13 (GCF_000001405.25)	11	NC_000011.9 (20621154..20680831)

Chromosome 11 - NC_000011.10 Genomic Context describing neighboring genes

Genomic regions, transcripts, and products

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Go to reference sequence details

Genomic Sequence:

Go to nucleotide: Graphics FASTA GenBank

Expression

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See details

Project title: HPA RNA-seq normal tissues HPA RNA-seq normal tissues
Description: RNA-seq was performed of tissue samples from 95 human individuals representing 27 different tissues in order to determine tissue-specificity of all protein-coding genes
BioProject: PRJEB4337
Publication: PMID 24309898
Analysis date: Wed Apr 4 07:08:55 2018

Bibliography

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GeneRIFs: Gene References Into Functions

What's a GeneRIF?

The allosteric inhibition of glycine transporter 2 by bioactive lipid analgesics is controlled by penetration into a deep lipid cavity.
Title: The allosteric inhibition of glycine transporter 2 by bioactive lipid analgesics is controlled by penetration into a deep lipid cavity.
Photoswitchable ORG25543 Congener Enables Optical Control of Glycine Transporter 2.
Title: Photoswitchable ORG25543 Congener Enables Optical Control of Glycine Transporter 2.
An overview of hyperekplexia-associated mutations in the neuronal glycine transporter 2 (GlyT2) with special focus on dominant mutations that effect the quaternary structure of GlyT2 (review).
Title: Hyperekplexia-associated mutations in the neuronal glycine transporter 2.
analysis of the human SLC6A5 gene mutation associated with hyperekplexia
Title: Molecular basis of the dominant negative effect of a glycine transporter 2 mutation associated with hyperekplexia.
Report that in the presence of a GlyT2 mechanism-based toxicity, reversible inhibitors might allow a tolerable balance between efficacy and toxicity.
Title: Reversible inhibition of the glycine transporter GlyT2 circumvents acute toxicity while preserving efficacy in the treatment of pain.
Constitutive endocytosis and turnover of the neuronal glycine transporter GlyT2 is dependent on ubiquitination of a C-terminal lysine cluster.
Title: Constitutive endocytosis and turnover of the neuronal glycine transporter GlyT2 is dependent on ubiquitination of a C-terminal lysine cluster.
A novel dominant hyperekplexia mutation Y705C alters trafficking and biochemical properties of the presynaptic glycine transporter GlyT2.
Title: A novel dominant hyperekplexia mutation Y705C alters trafficking and biochemical properties of the presynaptic glycine transporter GlyT2.
This study firmly establishes the combination of missense, nonsense, frameshift, and splice site mutations in the GlyT2 gene as the second major cause of startle disease.
Title: Mutations in the GlyT2 gene (SLC6A5) are a second major cause of startle disease.
A transgenic cell line is studied in which green fluorescent protein (GFP) is expressed under the control of the promoter for the glycine transporter GlyT2 during zebrafish development.
Title: Early glycinergic axon contact with the Mauthner neuron during zebrafish development.
Observational study of gene-disease association, gene-environment interaction, and pharmacogenomic / toxicogenomic. (HuGE Navigator)
Title: Influence of 5-HTTLPR polymorphism on resting state perfusion in patients with major depression.

Submit: New GeneRIF Correction See all GeneRIFs (16)

Phenotypes

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Find tests for this gene in the NIH Genetic Testing Registry (GTR)

Review eQTL and phenotype association data in this region using PheGenI

Associated conditions

Description	Tests
Hyperekplexia 3 MedGen: C3553288 OMIM: 614618 GeneReviews: Hereditary Hyperekplexia Overview	Compare labs

EBI GWAS Catalog

Description
Novel genetic loci identified for the pathophysiology of childhood obesity in the Hispanic population. EBI GWAS Catalog EBI GWAS CatalogPubMed

Variation

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See variants in ClinVar

See studies and variants in dbVar

See Variation Viewer (GRCh37.p13)

See Variation Viewer (GRCh38)

Interactions

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Products	Interactant	Other Gene	Complex	Source	Pubs	Description

General gene information

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Markers

D11S3601 (e-PCR)
- UniSTS:152839

D11S4114 (e-PCR)
- UniSTS:45576

SHGC-145762 (e-PCR)
- UniSTS:174774

G60550 (e-PCR)
- UniSTS:137656

Gene Ontology Provided by GOA

Function	Evidence Code	Pubs
enables glycine:sodium symporter activity	IBA Inferred from Biological aspect of Ancestor more info
enables glycine:sodium symporter activity	IDA Inferred from Direct Assay more info	PubMed
enables glycine:sodium symporter activity	IMP Inferred from Mutant Phenotype more info	PubMed
enables glycine:sodium symporter activity	TAS Traceable Author Statement more info
enables metal ion binding	IEA Inferred from Electronic Annotation more info

Process	Evidence Code	Pubs
involved_in chemical synaptic transmission	TAS Traceable Author Statement more info	PubMed
involved_in glycine import across plasma membrane	IBA Inferred from Biological aspect of Ancestor more info
involved_in glycine import across plasma membrane	IDA Inferred from Direct Assay more info	PubMed
involved_in neurotransmitter transport	IEA Inferred from Electronic Annotation more info
involved_in sodium ion transmembrane transport	IBA Inferred from Biological aspect of Ancestor more info
involved_in synaptic transmission, glycinergic	IBA Inferred from Biological aspect of Ancestor more info
involved_in synaptic transmission, glycinergic	IMP Inferred from Mutant Phenotype more info	PubMed

Component	Evidence Code	Pubs
located_in dense core granule	ISS Inferred from Sequence or Structural Similarity more info
located_in endosome	ISS Inferred from Sequence or Structural Similarity more info
located_in glycinergic synapse	IEA Inferred from Electronic Annotation more info
located_in membrane	TAS Traceable Author Statement more info	PubMed
is_active_in plasma membrane	IBA Inferred from Biological aspect of Ancestor more info
located_in plasma membrane	IDA Inferred from Direct Assay more info	PubMed
located_in plasma membrane	IMP Inferred from Mutant Phenotype more info	PubMed
located_in plasma membrane	TAS Traceable Author Statement more info
located_in presynaptic membrane	IEA Inferred from Electronic Annotation more info

General protein information

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Preferred Names: sodium- and chloride-dependent glycine transporter 2

Names: norepinephrine transporter 1; solute carrier family 6 (neurotransmitter transporter, glycine), member 5

NCBI Reference Sequences (RefSeq)

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RefSeqs maintained independently of Annotated Genomes

These reference sequences exist independently of genome builds. Explain

These reference sequences are curated independently of the genome annotation cycle, so their versions may not match the RefSeq versions in the current genome build. Identify version mismatches by comparing the version of the RefSeq in this section to the one reported in Genomic regions, transcripts, and products above.

Genomic

NG_013086.3 RefSeqGene

Range

5002..64679

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GenBank, FASTA, Sequence Viewer (Graphics)

mRNA and Protein(s)

NM_001318369.2 → NP_001305298.1 sodium- and chloride-dependent glycine transporter 2 isoform 2

Status: REVIEWED

Source sequence(s)

AC090707

UniProtKB/Swiss-Prot

Q9Y345

UniProtKB/TrEMBL

Q4VAM4

Conserved Domains (1) summary

cl00456
Location:1 → 553

SLC5-6-like_sbd; Solute carrier families 5 and 6-like; solute binding domain
NM_004211.5 → NP_004202.4 sodium- and chloride-dependent glycine transporter 2 isoform 1

Status: REVIEWED

Source sequence(s)

AC090707

Consensus CDS

CCDS7854.1

UniProtKB/Swiss-Prot

O95288, Q4VAM7, Q9BX77, Q9Y345

UniProtKB/TrEMBL

Q4VAM5, Q4VAM6

Related

ENSP00000434364.2, ENST00000525748.6

Conserved Domains (1) summary

cd11499
Location:191 → 787

SLC6sbd_GlyT2; Na(+)- and Cl(-)-dependent glycine transporter GlyT2; solute-binding domain

RefSeqs of Annotated Genomes: GCF_000001405.40-RS_2024_08

The following sections contain reference sequences that belong to a specific genome build. Explain

Reference GRCh38.p14 Primary Assembly

Genomic

NC_000011.10 Reference GRCh38.p14 Primary Assembly

Range

20599608..20659285

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GenBank, FASTA, Sequence Viewer (Graphics)

mRNA and Protein(s)

XM_017018544.3 → XP_016874033.1 sodium- and chloride-dependent glycine transporter 2 isoform X1

RNA

XR_007062528.1 RNA Sequence

Alternate T2T-CHM13v2.0

Genomic

NC_060935.1 Alternate T2T-CHM13v2.0

Range

20720301..20780085

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GenBank, FASTA, Sequence Viewer (Graphics)

mRNA and Protein(s)

XM_054370482.1 → XP_054226457.1 sodium- and chloride-dependent glycine transporter 2 isoform X2
XM_054370481.1 → XP_054226456.1 sodium- and chloride-dependent glycine transporter 2 isoform X1